Asymmetric superoxide release inside and outside the mitochondria in skeletal muscle under conditions of aging and disuse

Superoxide released from mitochondria forms reactive oxygen species that can cause severe oxidative damage and have been associated with aging- and disuse-induced muscle dysfunction. Superoxide is released to both the exterior and the matrix of mitochondria, where oxidative damage is not necessarily the same. This complicates determining the role of mitochondrial superoxide in eliciting oxidative stress in skeletal muscle. A newly developed capillary electrophoretic method analyzes hydroxytriphenylphosphonium ethidium, a superoxide-specific product of triphenylphosphonium hydroethidine, released to outside the mitochondria (supernatant) and retained in the matrix (pellet). In this study, we investigated the mitochondrial superoxide production of soleus (type I) and semimembranosus (type II) muscles of Fischer 344 rats affected by aging (13 vs. 26 mo) and disuse (hindlimb unloading). In agreement with previous studies, overall superoxide production increased with aging and disuse. On the other hand, the new experimental method revealed that superoxide production outside the mitochondria of the soleus does not show a significant age-related increase. Another observation was that the superoxide production increase in the matrix occurs earlier (7 days of disuse) compared with the outside mitochondria (14 days of disuse) in both muscle types. These findings indicate that superoxide release is complex as it occurs asymmetrically at both sides of the mitochondrial inner membrane, and that such release has muscle type and temporal specificity. These findings are important to refine current concepts on oxidative stress associated with muscle aging and disuse

Late-onset Caloric Restriction Alters Skeletal Muscle Metabolism by Modulating Pyruvate Metabolism

[[abstract]]Caloric restriction (CR) attenuates age-related muscle loss. However, the underlying mechanism responsible for this attenuation is not fully understood. This study evaluated the role of energy metabolism in the CR-induced attenuation of muscle loss. The aims of this study were twofold: 1) to evaluate the effect of CR on energy metabolism and determine its relationship with muscle mass, and 2) to determine whether the effects of CR are age dependent. Young and middle-aged rats were randomized into either 40% CR or ad libitum (AL) diet groups for 14 wk. Major energy-producing pathways in muscles, i.e., glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), were examined. We found that the effects of CR were age dependent. CR improved muscle metabolism and normalized muscle mass in middle-aged animals but not young animals. CR decreased glycolysis and increased the cellular dependency for OXPHOS vs. glycolysis in muscles of middle-aged rats, which was associated with the improvement of normalized muscle mass. The metabolic reprogramming induced by CR was related to modulation of pyruvate metabolism and increased mitochondrial biogenesis. Compared with animals fed AL, middle-aged animals with CR had lower lactate dehydrogenase A content and greater mitochondrial pyruvate carrier content. Markers of mitochondrial biogenesis, including AMPK activation levels and SIRT1 and COX-IV content, also showed increased levels. In conclusion, 14 wk of CR improved muscle metabolism and preserved muscle mass in middle-aged animals but not in young developing animals. CR-attenuated age-related muscle loss is associated with reprogramming of the metabolic pathway from glycolysis to OXPHOS

Diet-induced obesity accelerates blood lactate accumulation of rats in response to incremental exercise to maximum

[[abstract]]Blood lactate increases during incremental exercise at high-intensity workloads, and limited exercise capacity is a characteristic of obese animals. This study examined whether blood lactate changes in response to incremental exercise is disrupted in obese animals. Muscular and hepatic proteins that are critical in lactate metabolism were also investigated. Rats were randomized to either standard chow (control) or high-fat diet (HFD) groups. All animals underwent an incremental treadmill test after 14 wk of diet intervention. Blood lactate levels were measured before and after the treadmill test. Activities of mitochondrial oxidative phosphorylation and glycolysis were examined in muscle tissues. Proteins in the liver and skeletal muscles that participate in the turnover of blood lactate were determined by Western blot. Running time in the incremental treadmill test decreased in the HFD group, and blood lactate accumulated faster in these animals than in the control group. Animals with HFD had a decreased level of hepatic monocarboxylate transporter 2, the protein responsible for blood lactate uptake in the liver. Skeletal muscles of animals with HFD showed greater glycolytic activity and decreased content of lactate dehydrogenase B, which converts lactate to pyruvate. We conclude that blood lactate accumulated faster during incremental exercise in obese animals and was associated with their decreased exercise performance. Changes in the metabolic pattern of muscles and changes of liver and muscle proteins associated with lactate utilization likely contribute to the abnormal response of blood lactate to incremental exercise in obese animals

慢性中風病人的運動復健與營養增補策略：可能生理機制與實務應用初探 The rehabilitation exercise and nutrition/supplement strategy in chronic stroke survivor: Possible physiological mechanisms and practical applications

[[abstract]]腦中風（cerebral vascular accident, CVA）是慢性失能及影響日常生活功能的主因之一，因此以提昇患者身體功能的積極復健運動訓練日趨重要。研究證實，營養增補策略有助於提高運動訓練適應效果與運動表現。慢性中風患者（中風發生大於6個月）在積極進行復健運動訓練的同時，也有特殊營養需求，但目前探討的研究仍然不多。因此，本文將以運動訓練促進肌力與提高肌肉蛋白質合成為主軸，透過整合現有科學證據，逐節探討慢性中風患者在復健運動介入及營養補充的特殊需求。同時，進一步評析營養介入促進訓練適應之生理機制，並進行多種營養增補策略對中風復健運動訓練效果的初探。文獻回顧指出，阻力運動或耐力運動後，立即補充蛋白質營養（如：乳清蛋白或大豆蛋白），可使運動促進肌肉蛋白質合成效率產生加成效益，進而提高肌肉組織質量。最近的動物研究結果顯示，益生菌可預防神經功能退化的危險因子與促進運動訓練效益，同時天然多酚類化合物（如：兒茶素或白藜蘆醇）或維生素也可以降低動物中風後引起的氧化壓力傷害、促進神經組織增生。鑒於相關營養增補對促進神經修復與保護作用之議題仍以動物研究成果居多，因此確實效益仍有待後續人體研究進行證實。本文建議未來研究方向可朝向天然抗氧化物增補、益生菌、複合營養補充劑配方增補、及整合性人體臨床研究等方向進行後續探討。 ＂Cerebral vascular accident (CVA)＂ is one of the primary causes of functional disability and substantially affecting activities of daily living (ADL), thus constructive rehabilitation exercise training program is essential to improve physical performance and motor functionality recovery in the chronic stroke patients. Accumulative evidence has revealed that appropriate nutritional supplementation strategies, including the proper types and timing of nutrient provision, can additionally help to improve exercise training adaptations and physical performance. Chronic stroke patients (6-12 months after onset) have specific nutritional demands when they perform rehabilitation exercise resulting from their neurological impairments, whereas there are still few studies focusing on the potential enhancing effects of applying nutritional supplementation during stroke rehabilitation in this populations. Therefore, through integrating currently existing scientific evidence, this review here focus on the special demands of rehabilitation exercise training and nutritional supplementation in chronic stroke patients, and the underlying physiological mechanisms for the benefits of rehabilitation exercise training and potential nutritional interventions on promoting exercise training adaptations are explored and discussed as well. Recent literature suggests that ingestion of protein-based supplementation (e.g. whey protein or soy protein) immediately after resistance or endurance exercise can further elicit muscle protein accretion by increasing the efficiency of protein synthesis. Furthermore, recent animal studies have shown that probiotics can prevent aging-caused neurological degeneration and promote exercise training adaptations, and natural-sourced polyphenolic compounds (e.g., catechins, or resveratrol) and vitamins are also reported to reduce oxidative stress and to promote neurogenesis in the stroke animal models. However, it has to be noted that the potential neuroprotective and exercise performance-enhancing benefits of these novel nutraceutical supplements on these physical and neurological promoting effects are still mostly based on the findings obtained from animal research results. Therefore, the effectiveness, efficacy, and safety are still needed to be carefully investigated and verified through subsequent systemic human clinical trial studies. Taken together, the future research directions can focus on the potential benefits of natural antioxidants, probiotics, and formula of varied nutritional supplements, and more human clinical trial research are warranted to confirm the effectiveness of these nutritional interventions in the chronic stroke rehabilitation program

Anti-apoptotic and Pro-survival Effects of Food Restrictionon High-Fat Diet-induced Obese Hearts

[[abstract]]Food restriction and weight loss are known to prevent obesity-related heart diseases. This study investigates whether food restriction elicits anti-apoptotic and pro-survival effects on high-fat diet-induced obese hearts. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from three groups of Sprague-Dawley rats which were fed with regular chow diet (CON, 13.5 % fat), a high-fat ad libitum diet (HFa, 45 % fat), or a high-fat food-restricted diet (HFr, 45 % fat, maintaining the same weight as CON) for 12 weeks. Body weight, blood pressure, heart weight, triglycerides, insulin, HOMAIR, interstitial spaces, cardiac fibrosis, and cardiac TUNEL-positive apoptotic cells were increased in HFa relative to CON, whereas these parameters were decreased in HFr relative to HFa. The protein levels of cardiac Fas ligand, Fas receptors, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas receptor-dependent apoptotic pathways), as well as t-Bid/Bid, Bax/Bcl-2, Bad/p-Bad, Cytochrome c, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) in HFr were lower than those in HFa. Moreover, the Bcl-xL and IGF-1-related components of IGF-1, p-PI3 K/PI3 K, p-Akt/Akt in HFr were higher than those in HFa. Our findings suggest that a restricted high-fat diet for maintaining weight control could diminish cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways as well as might enhance IGF-1-related pro-survival pathways. In sum, food restriction for maintaining normal weight could elicit anti-apoptotic and pro-survival effects on high-fat diet-induced obese hearts